Light induced drug delivery into cancer cells
Light induced drug delivery into cancer cells
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DOI：
10.1016/j.biomaterials.2010.10.029
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发表时间：
2011-02-01
期刊：
影响因子：
14
通讯作者：
David, Ayelet
中科院分区：
文献类型：
--
作者：
Shamay, Yosi;Adar, Lily;David, Ayelet
细胞穿透肽(CPPs)可用于多种货物的细胞内递送，包括各种纳米药物载体。然而，所有CPP序列的阳离子性质，从而缺乏细胞特异性，限制了它们在体内的药物传递应用。在这里，我们设计并测试了一种策略，通过使用带有光活化笼状CPP(CCPP)的聚合物将染料和药物定位地输送到癌细胞中。在CPP穿透的最小序列((RRMKWKK58)-R-52)上，赖氨酸残基的正电荷被光可切割基团掩盖，以最小化非特异性吸附和细胞摄取。一旦被紫外光照射，这些保护基团被裂解，带正电的CPP恢复其活性，并促进聚合物-染料或聚合物-药物结合物在细胞内快速输送到癌细胞。我们发现，10分钟的光照时间足以增强带有促凋亡多肽(D)(KLAKLAK)(2)的聚合物-CPP结合物对80%的靶细胞的穿透性，并促进类似开关的细胞毒活性，使细胞存活率在2小时后从100%转变到10%。本报告为通过光激活细胞穿透性多肽进行细胞内药物输送而进行肿瘤靶向提供了一个例子。(C)2010爱思唯尔有限公司。保留所有权利。
Cell-penetrating peptides (CPPs) can be used for intracellular delivery of a broad variety of cargoes, including various nanoparticulate pharmaceutical carriers. However, the cationic nature of all CPP sequences, and thus lack of cell specificity, limits their in vivo use for drug delivery applications. Here, we have devised and tested a strategy for site-specific delivery of dyes and drugs into cancer cells by using polymers bearing a light activated caged CPP (cCPP). The positive charge of Lys residues on the minimum sequence of the CPP penetratin ((RRMKWKK58)-R-52) was masked with photo-cleavable groups to minimize non-specific adsorption and cellular uptake. Once illuminated by UV light, these protecting groups were cleaved, the positively charged CPP regained its activity and facilitated rapid intracellular delivery of the polymer-dye or polymer-drug conjugates into cancer cells. We have found that a 10-min light illumination time was sufficient to enhance the penetration of the polymer-CPP conjugates bearing the proapoptotic peptide, (D)(KLAKLAK)(2), into 80% of the target cells, and to promote a 'switch' like cytotoxic activity resulting a shift from 100% to 10% in cell viability after 2 h. This report provides an example for tumor targeting by means of light activation of cell-penetrating peptides for intracellular drug delivery. (C) 2010 Elsevier Ltd. All rights reserved.